This program project addresses the structure and function of the plasma mediation pathways including the scope of the coagulation protein pathways, the fibrinolytic and complement pathways and the anaphylatoxins. The initiation of the mediation pathways of the blood by monocytes and the amplification of pathways by receptor interactions and protein assembly are examined. The basic mechanisms of platelet cytoskeletal function, vertical assembly and platelet surface receptors are major topics. Protein interactions within the plasma and with vascular cells including platelets, leukocytes, lymphocytes, monocytes, endothelial cells, and vascular smooth muscle cells will be examined as well as the mechanisms of induction and regulation of various types of plasminogen activators and their inhibitors. The purpose of such diverse studies is to: 1) address the important goals intrinsic to each project, but even more to: 2) develop the information in a setting where it is possible to gain overall perspective and analyze the integrated interactions between all each these facets of the blood and vasculature that represent the basis of hemostatic, thrombotic and inflammatory diseases of the blood and vasculature.